Green Synthesis of 1,5-Benzodiazepines with Multifunctional Groups

Abstract

1,5-Benzodiazepine compounds are seven-membered nitrogen heterocyclic compounds with important biological and pharmacological activities. Ester group, carboxyl group, acyl group and aryl group are active groups of 1,5-benzodiazepine compounds. One-pot green synthesis of 34 kinds of 1,5-benzodiazepines with COR, COOR or COOH by three-component tandem reaction was performed at room temperature (25 ℃) with a yield of up to 90%. The mechanism of catalytic tandem reaction was proposed. These reactions were achieved by using aldehyde carbonyl compounds or dicarbonyl compounds, 3-butyn-2-one, substituted o-phenylenediamine as raw materials, absolute ethanol as solvent, magnetic nano cobalt ferrite (CoFe2O4) was realized under catalyst or without catalyst. The multifunctional 1,5-benzodiazepine compounds were formed via Michael addition reaction, nucleophilic addition-dehydration reaction, intramolecular imine-enamine cyclization and proton transfer processes, which realized that multiple active groups such as active acyl, ester or carboxyl groups were simultaneously introduced into the seven-membered ring of the benzodiazepine in a reaction system under mild conditions. This synthesis method has the advantages of novel synthesis method, atom economy, high yield and selectivity of the target compounds, which realize the green reaction process, and provide a new idea for green synthesis of benzozazepines. Keywords three-component tandem reaction; green synthesis; 1,5-benzodiazepine compounds 1,5-苯并二氮杂䓬及其衍生物是一类具有生物活性 的含氮杂环化合物 [1][2][3] . 由于具有特权结构的分子骨架, 在不同位置和距离"接枝"活性功能基团可形成不同的 药效团配置 [4][5][6][7][8][9] , 可与不同的受体结合, 产生不同的药理 作用. 因此是许多天然产物和药物分子的骨架, 它们具 有抗焦虑 [10] 、抗抑郁 [11] 、抗炎 [12] 、镇痛 [13] 及催眠 [14] 等 多种生物活性, 是新药研发中一类有价值的活性化合 物. 多年来, 经过大量的研究和探索, 一些活性 1,5-苯 并氮杂䓬类化合物已经成为治疗神经系统疾病的有效 药物 [15][16][17] . 研究表明酯基(COOR)、羧基(COOH)、酰基